Infection by Listeria monocytogenes provides an excellent model for study of the complexities of the immune response to intracellular pathogens. Cell mediated immunity, particularly CD8+ T cells, are required for control of Listeria infection, probably due to its intracellular niche and its ability to escape from cellular phagosomes into the cytoplasm of host cells. Most proteins made by Listeria are retained inside the organism, separated from the MHC class I processing pathway by the bacterial membrane. As secreted proteins would be most readily accessible to class I peptide processing pathways it is suggested that the Listeria proteins most important for inducing protective CD8 T cells are secreted. Experiments are proposed to address this hypothesis by: 1) identifying new L. monocytogenes antigens that elicit CD8 T cells after in vivo infection; 2) assessing the in vivo protective capacity of CD8 T cells specific for L. monocytogenes antigens expressed in different bacterial compartments; and 3) testing the ability of CD8 T cells to mediate immunity against L. monocytogenes expressing the same CD8 T cell antigen in different bacterial compartments. The ability of T cells derived from infected mice and directed against antigens expressed in distinct bacterial compartments to protect mice from infection will be determined.